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. 2016 Jul;62(5):535-543.
doi: 10.18097/PBMC20166205535.

[Conformational polymorphysm of G-rich fragments of DNA ALU-repeats. I. Potential noncanonical structures]

[Article in Russian]
A V Sekridova  1 , A M Varizhuk  1 , O N Tatarinova  1 , V V Severov  1 , N A Barinov  1 , I P Smirnov  1 , V N Lazarev  1 , D V Klinov  1 , G E Pozmogova  1
Affiliations

[Conformational polymorphysm of G-rich fragments of DNA ALU-repeats. I. Potential noncanonical structures]

[Article in Russian]
A V Sekridova et al. Biomed Khim. 2016 Jul.

Abstract
in English, Russian

In this paper, we report results of systematic studies of conformational polymorphism of G-rich DNA fragments from Alu repeats. Alu retrotransposones are primate-specific short interspersed elements. Using the Alu sequence from the prooncogen bcl2 intron and the consensus AluSx sequence as representative examples, we determined characteristic Alu sites that are capable of adopting G-quadruplex (GQ) conformations (i.e., potential quadruplex sites - PQSAlu), and demonstrated by bioinformatics methods that those sites are Alu-specific in the human genome. Genomic frequencies of PQSAlu were assessed (~1/10000 b.p.). The sites were found to be characteristic of young (active) Alu families (Alu-Y). A recombinant DNA sequence bearing the Alu element from the human bcl2 gene (304 b.p.) and its PQS-mutant (Alu-PQS) were constructed. The formation of noncanonical structures in Alubcl2 dsDNA and the absence of such structures in the case of Alu-PQS were shown using DMS-footprinting and AFM microscopy. Expression vectors bearing wild-type and mutant Alu insertions in the promoter regions were obtained, and the effects of these insertions on the expression of the reporter gene in НЕК293 and HeLa cell lines were compared. Our findings on the spatial organization of Alu repeats may provide insight into the mechanisms of genomic rearrangements which underlie many oncological and neurodegenerative diseases.

Vpervye sistemno rassmotren konformatsionnyĭ polimorfizm G-bogatykh fragmentov Alu-povtorov DNK (Alu). Retrotranspozony Alu – korotkie dispergirovannye povtory, shiroko predstavlennye v genomakh primatov. Na primere posledovatel'nosteĭ Alu-introna proonkogena bcl2 i konsensusnogo AluSx metodom bioinformaticheskogo analiza opredeleny kharakternye saĭty (PQS), sposobnye formirovat' G-kvadrupleksy (GQ). Pokazano, chto v genome cheloveka oni assotsiirovany prakticheski iskliuchitel'no s Alu-povtorami. Costavleno predstavlenie o chastotakh vstrechaemosti PQSAlu (~1/10000 p.n.); ustanovleno, chto oni naibolee kharakterny dlia molodykh (aktivnykh) semeĭstv AluY-povtorov. Polucheny rekombinantnye posledovatel'nosti Alu gena bcl2 (304 p.n.) i mutant Alu-PQS. Metodami DMS-futprintinga i atomno-silovoĭ mikroskopii (ACM) pokazana realizatsiia nekanonicheskikh struktur v sostave DNK Alubcl2 i ikh otsutstvie v Alu-PQS. Polucheny ékspressionnye vektory, nesushchie vstavki prirodnogo i mutantnogo Alu v promotornoĭ oblasti reporternogo gena, i sopostavleny ikh reguliatornye éffekty pri transfektsii kul'tur kletok NEK293 i HeLa. My predpolagaem, chto izuchenie dinamiki prostranstvennoĭ organizatsii Alu-povtorov DNK mozhet vnesti vklad v ponimanie mekhanizmov genomnykh perestroek, lezhashchikh v osnove mnogikh onkologicheskikh i neĭrodegenerativnykh patologiĭ.

Keywords: Alu-repeats; G-quadruplex DNA; dynamics of DNA secondary structures.

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